RT Journal Article
SR Electronic
T1 A Hidden Markov Model Combining Linkage and Linkage Disequilibrium Information for Haplotype Reconstruction and Quantitative Trait Locus Fine Mapping
JF Genetics
JO Genetics
FD Genetics Society of America
SP 789
OP 798
DO 10.1534/genetics.109.108431
VO 184
IS 3
A1 Druet, Tom
A1 Georges, Michel
YR 2010
UL http://www.genetics.org/content/184/3/789.abstract
AB Faithful reconstruction of haplotypes from diploid marker data (phasing) is important for many kinds of genetic analyses, including mapping of trait loci, prediction of genomic breeding values, and identification of signatures of selection. In human genetics, phasing most often exploits population information (linkage disequilibrium), while in animal genetics the primary source of information is familial (Mendelian segregation and linkage). We herein develop and evaluate a method that simultaneously exploits both sources of information. It builds on hidden Markov models that were initially developed to exploit population information only. We demonstrate that the approach improves the accuracy of allele phasing as well as imputation of missing genotypes. Reconstructed haplotypes are assigned to hidden states that are shown to correspond to clusters of genealogically related chromosomes. We show that these cluster states can directly be used to fine map QTL. The method is computationally effective at handling large data sets based on high-density SNP panels.